Neurotoxins Flashcards
Describe the mechanism of action of bromethalin
Uncouples oxidative phosphorylation in the brain and liver.
Decreases ATP production —> increases lipid peroxidation —> affects the cellular sodium and potassium pumps —> lead to sodium accumulation in the cell —> edema of the CNS
What are the clinical signs expected with bromethalin ingestion
Clinical signs can usually be seen 2-24 hours after ingestion.
Clinical signs possible
- Anisocoria, nystagmus, changes in PLR
- Change in behaviour, depression
- Hyperesthesia, tremors.
- Ataxia, paresis, hind limb paralysis.
- Seizure, coma.
Describes the mechanism of action of the organophosphate and carbamate
Inhibits acethylcholinesterase activity —> lead to built up of acetylcholine in the synaptic cleft —> lead to overstimulation of the cholinergic nerves.
Reversible : carbamate
Irreversible : organophosphate.
What are the clinical signs to be expected with organophosphate / carbamate toxicity ?
Overstimulation of the skeletal muscle and the parasympathetic nervous system.
What ticks can cause tick paralysis
American dog tick : Dermacentor variabilis
Rocky Mountain wood tick : Dermacentor andersoni
Describe the mechanism of tick paralysis
Dermacentor virabilis and andersoni secretes a salivary neurotoxin that interferes with release of Ach —> revere blockade of neuromuscular junctions.
What are the clinical signs associated with tick paralysis
Acute clinical signs.
Ascending, flaccid, afebrile motor paralysis with preserved sensation.
Generally the hind limbs are affected first and then the forelimbs are affected.
How is botulism toxin transmitted
Ingestion of spoiled food containing the endotoxin or carrion that producing the bacteria Clostridium botulinum.
Describe the mechanism of action of the botulinum toxin
Toxin is absorbed in the small intestine via endocytosis —> enters the lymphatic system and then the blood stream.
The botulism heavy chains binds rapidly and with high affinity to the pre synaptic neuronal cell receptor —> endosomal internalization of the toxin —> membrane translocation —> modification of SNARE protein (required for exocytosis of Ach ant the neuromuscular junction.
What are the clinical signs associated with botulism
Flaccid paralysis affecting the limbs, trunk and head muscles.
Evidence of autonomic nervous system dysfunction.
Describe the mechanism of action of action of tetanus
The tetanus spores are introduced into wounds via penetrating injuries.
Tetanus bacillus secretes 2 endotoxins —> tetanospasmin and tetanolysin.
Tetanolysin : causes local damage to otherwise viable tissues surrounding the infected area.
Tetanospasmin.
- Heavy chain: high affinity for the ganglioside surface on the neuromuscular end-plate —> responsible for internalization, cytosolic translocation and fast retrograde axonal transport of the light chain.
- Light chain: acts presymaptically to prevent release of the neurotransmitter —> cleaves and inactivate synaptobrevin (necessary for docking and fusion of the neurotransmitter vesicles).
Amphetamine
Mechanism of action : Stimulates the release of cathecholamines from the adrenal glands, cerebral cortex, medullary respiratory center and reticular activating system.
Clinical sings : cardiac and CNS stimulation within 1-2 hours after infection. May include hyperactivity, mydriasis, hyperthermia, tachycardia, lactic acidosis, hypertension and rarely seizures.
Methylphenidate
Inhibit noradrenaline and dopamine reuptake by the nerve terminus. Peak effect 30-45 min after dosing.
Clinical signs include agitation, hyperactivity, pacing, clinging, inappropriate urination, circling, excitation, lethargy, anxiety, muscle fasciculation and tremor. Passible CNS depression an ataxia.
Cardiopulmonary and digestive systems are also frequently affected.
Methylxantine caffein
Mechanism is unknown (adenosine antagonism, increased catecholamine release, increased calcium release ?)
Clinical signs : usually develop within several hours of ingestion, may include vomiting (usually the first sign), restlessness, hyperactivity, ataxia, muscle tremor, tachycardia, cardiac arrhythmia, seizure, PU/PD, hyperthermia, cyanosis and coma.
Permethrin and other pyrethrin and pyrethroid insecticids
Interference with sodium channels, enhances sodium ion conductance and possible post synaptic GABA receptor-chloride ionophore complex blocade.
Principally toxic in cats. Toxicosis generally develops within hours of exposure, but may be delayed as a result of of prolonged exposure form dermal absorption or grooming.
initial clinical signs associated with the application include paresthesia —> ear twitching, paw and tail flicking, hyperexcitability and hyperesthesia.
More severe clinical signs incude muscle tremors, increased salivation, ataxia, vomiting, CNS depression, hyperexcitability or hyperactivity, seizure, dyspnea or death
